Thrombosis and hemostasis testing is the in vitro study of the ability of the blood to form clots and to break clots in vivo. As thrombotic and hemostasis pathways form a part of very important disease states ranging from hemophilia to strokes and heart attacks, the testing of a patients capabilities in thrombosis and hemostasis is a critical diagnostic tool. Should a patients ability to form clots in vitro fall outside of the established norm, or should certain markers be out of the normal range, the serum or plasma sample is further assayed to determine the reason for the problem. These assays are in standard use in all hospital laboratories.
Coagulation assays began, and are still done in many instances, in a test tube using hand methods. Early on, the goal was to determine if a patients blood sample would clot after certain materials were added. It was later determined that the amount of time it took for the sample to clot was related to congenital or acquired disorders. This type of testing is extremely dependent on the laboratory technologist, and so, some form of standardization was seen to be needed. As technology improved and stronger correlations between in vivo conditions and in vitro assays were established, semi-automatic coagulation analyzers began to appear.
These coagulation analyzers primary usefulness is to remove the subjectiveness in determining the exact second a clot forms in a sample in vitro. However, these analyzers did and do not have the automation required to remove variability associated with sample preparation. Furthermore, advances in clinical thrombosis and hemostasis assays resulted in the development of new types of assays that aided in the diagnosis and treatment of a patient and semi-automated coagulation analyzers seldom possess the ability to perform more than one assay at a time. This is because reagent pathways are dedicated to a single reagent, resulting in a limited number of assays that can be performed on each instrument. Generally, the semi-automated instrumentation performs one test in a batch mode, maintaining one profile of temperature vs. time for each different type of assay.
Semi-automated analyzers also require the technician to manually deliver the plasma sample. A new sampling device, generally a pipette tip, is used for each specimen to eliminate plasma cross-contamination between samples. Using a common sampling means for reagents and samples requires novel approaches to eliminate cross contamination of samples and reagents.
In order to have the next generation of analyzers, fully automated analyzers must be developed to be able to use the same sampling device for all specimens and to have common pathways for delivery of multiple reagents, and to provide a universal time and temperature profile compatible with a multitude of assays.
Additionally, any complex computations needed to be performed for an assay are done by an operator when semi-automated analyzers are used. Differences in operators techniques in analyzing data lead to increased levels of inaccuracy of the data. Another feature needed to improve coagulation testing is improved and standardized data analysis techniques to obtain the desired performance characteristics from inter and intra laboratory comparisons, which would result in a higher standard of care for the patient.
Quality control and system monitoring of the semi-automated coagulation analyzers are primitive and inadequate when compared to the state of the art.
The next generation of analyzers, a fully automated thrombosis and hemostasis analyzer, requires a statistically controlled, on-line quality assurance program that monitors the system integrity, as the analysis are being performed. This program must not only identify failures after they have occurred, but predict potential failures before they occur.
Another area of the clinical laboratory, the clinical chemistry laboratory, has had fully automated analyzers for a number of years. The tests performed and the types of reactions read, including colorimetric, fluorescent and luminescent measurement, are substantially different and have endpoints that are easier to detect than do coagulation-based tests, those performed in the coagulation laboratory. The same progress towards full automation has not been seen in the coagulation laboratory as in the clinical chemistry laboratory.
In general, the basic tests or assays performed in the coagulation laboratory using plasma, serum or whole blood include performing the Partial Thromboplastin Time ("PTT"), the Prothrombin Time ("PT"), the Activated Partial Thromboplastin Time ("APTT"), testing for deficiencies in Factors such as Factors II, V, VII, VIII, IX, XI, XII and others, and chromogenic and immunological testing for thrombosis or hemostasis markers. These, among others, have proven to be much more difficult to do on automated equipment than have the clinical chemistry tests. This is because the tests run in the coagulation laboratory usually: (1) involve unique time/temperature profiles; (2) are extremely sensitive to both reagent and plasma carryover; (3) require unique data analysis; and (4) have unique quality control requirements.
A method for automatically performing a variety of coagulation-related assays and a fully automated coagulation analyzer is needed to perform a host of assays in a totally random format that would expedite patient diagnosis. It must have the ability to control the sample preparation stages of an in vitro assay; to perform all thrombosis and hemostasis assays using a common temperature profile; to measure the reaction that occurs when the appropriate materials are added; and to determine both the immediate response as well as to provide mathematical tools for calculating complex results. This entire process should be monitored using an on-line quality control package that is designed to minimize imprecision associated with random error and to minimize bias associated with error due to the system itself, systemic error.
This type of fully automated coagulation analyzer would provide more accurate results that in turn would allow for quicker and more accurate diagnosis of current or predicted illness, thereby allowing for better treatment of the patient.